摘要
帕金森病(Parkinson disease,PD)是一种复杂的中枢神经系统退行性疾病,主要病理特征为黑质致密部多巴胺神经元的进行性丧失.目前PD主要治疗手段包括药物和手术.但药物存在神经保护活性不足、缺乏对因治疗、晚期无药可用等问题,手术治疗风险较大.近年来,细胞重编程技术取得突破性进展,由重编程产生的诱导多能干细胞(induced pluripotent stem cells,iPSCs)、诱导多巴胺神经元(induced dopamine neurons,iDNs)和诱导神经干细胞(induced neural stem cells,i NSCs)可用于治疗PD.移植iPSCs分化而来的多巴胺能神经元、iDNs和iNSCs至相应脑区,可起到神经替代与修复作用,有效治疗PD.本文重点介绍细胞重编程的机制,总结iPSCs、iDNs和iNSCs治疗PD的优缺点,并阐述尚存在的挑战,探讨可能的解决方案.
Parkinson disease(PD)is a complex neurodegenerative disorder of the central nervous system(CNS),the core pathological hallmark of which is the progressive loss of dopamine neurons in the substantia nigra pars compacta.At present,the main treatments of PD include drugs and surgery.However,the drugs lack enough neuroprotective activity,etiological treatment,and are not available in the later period,and the risk of surgery is high.Recently,cellular reprogramming technologies have made breakthrough developments.Induced pluripotent stem cells(iPSCs),induced dopamine neurons(iDNs)and induced neural stem cells(iNSCs)which are generated through reprogramming can be applied to treatment of PD.Transplantation of dopaminergic neurons differentiated from iPSCs,iDNs and iNSCs to specific brain regions can replace the lost neurons or restore the functional integrity of neurons,thus providing an effective treatment for PD.This article introduces mechanisms of cellular reprogramming,and summarizes advantages,disadvantages and efficacy of iPSCs,iDNs and iNSCs in the treatment of PD.It also explains current challenges and discusses the possible solutions.
作者
李玲洁
崔巍
徐淑君
王钦文
LI Ling-Jie;CUI Wei;XU Shu-Jun;WANG Qin-Wen(Zhejiang Provincial Key Laboratory of Pathophysiology,School of Medicine,Ningbo University,Ningbo 315211,China)
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2020年第10期1021-1031,共11页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金-新疆联合基金重点支持项目(U1503223)
宁波市“科技创新2025”重大专项(2019B10034)
宁波大学王宽诚幸福基金资助项目。
关键词
帕金森病
细胞重编程
诱导多能干细胞
诱导多巴胺神经元
诱导神经干细胞
移植
多巴胺能神经元
Parkinson disease
cellular reprogramming
induced pluripotent stem cells
induced dopamine neurons
induced neural stem cells
transplantation
dopaminergic neurons